The present invention generally relates to methods of treatment of sinusitis and otitis media (including otitis media with effusion and persistent middle ear effusion) involving the administration of a therapeutically effective amount of an antihistamine. It specifically relates to such treatment involving the administration of a therapeutically effective amount of loratadine or its metabolic derivative known as descarboethoxyloratadine (also referred to as desloratadine or xe2x80x9cDCLxe2x80x9d). The invention disclosed herein is related to that disclosed in pending U.S. Patent application, Serial No. 60/068,638, filed Dec. 23, 1997.
Sinusitis is the most frequently reported chronic disease in the United States, affecting more than 14% of the population. Sinusitis is an inflammation of the mucosa of the paranasal sinuses. Generally, there is an allergic cause to sinusitis. Otitis media, like sinusitis, is also generally considered to have an allergic cause. These are also characterized by retention of thickened respiratory secretions; however, the inflammation is manifest in the ear rather than in the sinuses. A discussion of sinusitis and otitis media can be found in Conn""s Current Therapy, 235 (1997); Diseases of the Sinusesxe2x80x94A Comprehensive Textbook of Diagnosis and Treatment, ed. M. E. Gershwin et al, Human Press, Totowa, N.J., pages 151-157 (1996); and Allergy-Principles and Practice, Volume II, ed. E. Middleton, Jr. et al, Mosby-Year Book, Inc., New York, pages 1027-1033 (1998). Also, a review of sinusitis and related facts is given by Z. Pelikan, xe2x80x9cThe Role of Allergy in Sinus Diseasexe2x80x9d, Clinical Reviews in Allergy and Immunology 16, 55-156 (1998).
Sinusitis and otitis media are often typically treated as an infectious disease. The treatment typically includes administration of an antibiotic along with a corticosteroid and an antihistamine, or a nasal decongestant, such as described in, for example, J. Braun et al, Allergy, 52 (6), 650-655 (1997). There are, however, occasions, when the sinusitis or otitis media is not necessarily accompanied by an infection. This is particularly true when the disease is associated with allergic rhinitis. At those times, administration of an antibiotic may not be needed. Physicians, however, do not generally administer antihistamines for these indications without accompanying antibiotic. This has been so since earlier known antihistamines, among other things, were anticholinergic, drying nasal secretions. Although antihistamines with far less anticholinergic activity are now available, no attempt to treat sinusitis or otitis media with administration of substantially non-sedating antihistamine with non-anticholinergic or reduced anticholinergic activity and without accompanying antibiotics has been reported.
It would be desirable to find methods of treatment for non-infective sinusitis or otitis media using an effective amount of substantially an antihistamine as an active ingredient in the absence of antibiotics.
It would be further desirable to find methods of treatment for non-infective sinusitis or otitis media using an effective amount of substantially an antihistamine with reduced anticholinergic activity as an active ingredient in the absence of antibiotics.
Other desires, objectives and advantages of the present invention will be apparent o those skilled in the art from the accompanying description and claims.
The above-noted desires and objectives are addressed by the present invention which, in one embodiment, provides methods and pharmaceutical compositions for the treatment of non-infectious sinusitis or otitis media or both. The composition comprises in combination: (i) a therapeutically effective amount of one or more antihistamines with substantially reduced anticholinergic activity or a pharmaceutically acceptable salt or solvate of such antihistamine(s) and (ii) a pharmaceutically acceptable carrier. While additional ingredient or ingredients may optionally be present, the antihistamine(s) is (are) the major active ingredient(s) in the composition. Antibiotics, however, are absent in the composition. The antihistamines useful in the practice of the present invention correspond to the general Formula I: 
wherein X represents a halogen atom or a hydrogen atom; and Y represents hydrogen, xe2x80x94COOR1 or xe2x80x94SO2R2, wherein R1 represents a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic ring; and R2 represents a substituted or unsubstituted cycloalkyl group, or substituted or unsubstituted aryl group. The compounds of Formula I embrace optical isomers and mixtures thereof, racemic mixtures, enol forms and other such modifications. Preferred compounds belonging to Formula I are those in which X is a halogen atom or a hydrogen atom, and Y is hydrogen or xe2x80x94COOR1, where R1 is defined above. More particularly preferred compounds of this class are when X is Cl and R1 is carboethoxy (the compound being commonly known as loratadine or SCH 29851) and when X is Cl and R1 is hydrogen (the compound being commonly known as descarboethoxyloratadine or desloratadine or DCL or SCH 34117).
The antihistamine or its pharmaceutically acceptable salt or solvate is generally present in the composition in about 2.5-20 milligrams, preferably in about 5-10 milligrams and typically in about 7.5 milligrams per dosage. Additionally, a pharmaceutically acceptable carrier is present. As stated earlier, one or more other non-antibiotic ingredients may also be optionally present in the composition. Such optional compounds may include, a decongestant (such as, for example, pseudoephedrine), a cough suppressant (such as, for example, dextromethorphan), an expectorant (such as, for example, guiaifenesin), a leukotriene antagonist (such as, for example, montelukast or a pharmaceutically acceptable salt or solvate thereof, and the like), an inhaled nasal steroid (such as, for example, mometasone furoate, NASONEXxe2x80xa2 (available from Schering-Plough Corporation, Madison, N.J.) and the like), a non-steroidal anti-inflammatory (such as, for example, ibuprofen, naproxen and the like), a non-narcotic analgesic (such as, for example, acetaminophen and the like) and suitable combinations thereof.
The present invention additionally discloses a method for the treatment of non-infectious sinusitis and/or otitis media in a mammalian organism in need of such treatment, such treatment comprising administering a pharmaceutical composition described above.